Publications by authors named "Christopher Coleman"

68 Publications

Tuning Magnetic Properties of a Carbon Nanotube-Lanthanide Hybrid Molecular Complex through Controlled Functionalization.

Molecules 2021 Jan 22;26(3). Epub 2021 Jan 22.

Nano-Scale Transport Physics Laboratory, School of Physics, University of the Witwatersrand, Johannesburg Wits 2050, South Africa.

Molecular magnets attached to carbon nanotubes (CNT) are being studied as potential candidates for developing spintronic and quantum technologies. However, the functionalization routes used to develop these hybrid systems can drastically affect their respective physiochemical properties. Due to the complexity of this systems, little work has been directed at establishing the correlation between the degree of functionalization and the magnetic character. Here, we demonstrate the chemical functionalization degree associated with molecular magnet loading can be utilized for controlled tuning the magnetic properties of a CNT-lanthanide hybrid complex. CNT functionalization degree was evaluated by interpreting minor Raman phonon modes in relation to the controlled reaction conditions. These findings were exploited in attaching a rare-earth-based molecular magnet (Gd-DTPA) to the CNTs. Inductively coupled plasma mass spectrometry, time-of-flight secondary ion mass spectrometry and super conducting quantum interference device (SQUID) measurements were used to elucidate the variation of magnetic character across the samples. This controlled Gd-DTPA loading on the CNT surface has led to a significant change in the nanotube intrinsic diamagnetism, showing antiferromagnetic coupling with increase in the Weiss temperature with respect to increased loading. This indicates that synthesis of a highly correlated spin system for developing novel spintronic technologies can be realized through a carbon-based hybrid material.
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http://dx.doi.org/10.3390/molecules26030563DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7866014PMC
January 2021

Determining How Coronaviruses Overcome the Interferon and Innate Immune Response.

Methods Mol Biol 2020 ;2203:223-229

School of Life Sciences, Queens Medical Centre, University of Nottingham, Nottingham, UK.

All viruses have to overcome the innate immune response in order to establish infection. Methods have been developed to assay if, and how, viruses overcome these responses, and many can be directly applied to coronaviruses. Here, in vitro methods to determine how coronaviruses overcome this response are described.
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http://dx.doi.org/10.1007/978-1-0716-0900-2_16DOI Listing
March 2021

Broad Anti-coronavirus Activity of Food and Drug Administration-Approved Drugs against SARS-CoV-2 and SARS-CoV .

J Virol 2020 10 14;94(21). Epub 2020 Oct 14.

Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland, USA

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in China at the end of 2019 and has rapidly caused a pandemic, with over 20 million recorded COVID-19 cases in August 2020 (https://covid19.who.int/). There are no FDA-approved antivirals or vaccines for any coronavirus, including SARS-CoV-2. Current treatments for COVID-19 are limited to supportive therapies and off-label use of FDA-approved drugs. Rapid development and human testing of potential antivirals is urgently needed. Numerous drugs are already approved for human use, and subsequently, there is a good understanding of their safety profiles and potential side effects, making them easier to fast-track to clinical studies in COVID-19 patients. Here, we present data on the antiviral activity of 20 FDA-approved drugs against SARS-CoV-2 that also inhibit SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV). We found that 17 of these inhibit SARS-CoV-2 at non-cytotoxic concentrations. We directly followed up seven of these to demonstrate that all are capable of inhibiting infectious SARS-CoV-2 production. Moreover, we evaluated two of these, chloroquine and chlorpromazine, using a mouse-adapted SARS-CoV model and found that both drugs protect mice from clinical disease. There are no FDA-approved antivirals for any coronavirus, including SARS-CoV-2. Numerous drugs are already approved for human use that may have antiviral activity and therefore could potentially be rapidly repurposed as antivirals. Here, we present data assessing the antiviral activity of 20 FDA-approved drugs against SARS-CoV-2 that also inhibit SARS-CoV and MERS-CoV We found that 17 of these inhibit SARS-CoV-2, suggesting that they may have pan-anti-coronaviral activity. We directly followed up seven of these and found that they all inhibit infectious-SARS-CoV-2 production. Moreover, we evaluated chloroquine and chlorpromazine using mouse-adapted SARS-CoV. We found that neither drug inhibited viral replication in the lungs, but both protected against clinical disease.
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http://dx.doi.org/10.1128/JVI.01218-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7565640PMC
October 2020

Comorbid diabetes results in immune dysregulation and enhanced disease severity following MERS-CoV infection.

JCI Insight 2019 10 17;4(20). Epub 2019 Oct 17.

Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland, USA.

Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012 in Saudi Arabia and has caused over 2400 cases and more than 800 deaths. Epidemiological studies identified diabetes as the primary comorbidity associated with severe or lethal MERS-CoV infection. Understanding how diabetes affects MERS is important because of the global burden of diabetes and pandemic potential of MERS-CoV. We used a model in which mice were made susceptible to MERS-CoV by expressing human DPP4, and type 2 diabetes was induced by administering a high-fat diet. Upon infection with MERS-CoV, diabetic mice had a prolonged phase of severe disease and delayed recovery that was independent of virus titers. Histological analysis revealed that diabetic mice had delayed inflammation, which was then prolonged through 21 days after infection. Diabetic mice had fewer inflammatory monocyte/macrophages and CD4+ T cells, which correlated with lower levels of Ccl2 and Cxcl10 expression. Diabetic mice also had lower levels of Tnfa, Il6, Il12b, and Arg1 expression and higher levels of Il17a expression. These data suggest that the increased disease severity observed in individuals with MERS and comorbid type 2 diabetes is likely due to a dysregulated immune response, which results in more severe and prolonged lung pathology.
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http://dx.doi.org/10.1172/jci.insight.131774DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6824443PMC
October 2019

Upsloping lateral sourcil: a radiographic finding of hip instability.

J Hip Preserv Surg 2018 Dec 1;5(4):435-442. Epub 2018 Dec 1.

Department of Orthopaedics, University of Colorado School of Medicine, Aurora, CO, USA.

While radiographic findings of frank hip dysplasia are well defined, there is a lack of diagnostic criteria for patients with radiographically 'normal' hips who have borderline morphologic deficits and clinical instability. In this study, we aim to define and validate a new radiographic finding associated with hip instability known as the upsloping lateral sourcil (ULS). Patients (316) were reviewed for lateral center edge angles, generalized joint laxity assessed with the Beighton Hypermobility Score and the presence of the ULS. The ULS was defined as a caudal-to-cranial inclination of the middle-to-far lateral aspect of the acetabular sourcil with loss of the normal lateral acetabular concavity. The prevalence of the ULS correspondingly increased with the degree of under-coverage as defined by LCEA. Within the normal coverage group, hips with a ULS had smaller LCEAs than those without ULS (29° versus 32°,  < 0.001). Among hips with a ULS, 59.00% had generalized joint laxity. The association between the ULS finding and generalized joint laxity was statistically significant ( < 0.01). The ULS is seen with higher prevalence in patients with clinical hip laxity and radiographically decreasing LCEA and may serve as an adjunctive finding in patients presenting with hip pain and instability. The ULS may help to characterize patients with borderline hip dysplasia and laxity that fall outside conventional imaging criteria for dysplasia.
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http://dx.doi.org/10.1093/jhps/hny042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6328756PMC
December 2018

Effect of an Energy-Restricted, Nutritionally Complete, Higher Protein Meal Plan on Body Composition and Mobility in Older Adults With Obesity: A Randomized Controlled Trial.

J Gerontol A Biol Sci Med Sci 2019 05;74(6):929-935

Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina.

Background: Increasing protein content of the diet might be an effective strategy to preserve muscle mass in older adults undergoing caloric restriction, thereby preserving muscle function.

Methods: Ninety-six older adults (70.3 ± 3.7 years, 74% women, 27% African American) with obesity (35.4 ± 3.3 kg/m2; 47% total body fat) were randomized to a 6-month higher protein (providing 1.2-1.5 g/kg/d) weight loss (WL) program, utilizing the Medifast 4&2&1 Plan, or to weight stability (WS). Dual-energy x-ray absorptiometry-acquired total body mass and composition, and fast gait speed over 400 m was assessed at baseline, 3, and 6 months.

Results: At baseline, dual-energy x-ray absorptiometry-acquired total body, fat, and lean masses were 95.9 ± 14.6, 44.6 ± 7.6, and 48.7 ± 9.5 kg, respectively, and 400-m gait speed was 1.17 ± 0.20 m/s. Total body mass was significantly reduced in the WL group (-8.17 [-9.56, -6.77] kg) compared with the WS group (-1.16 [-2.59, 0.27] kg), with 87% of total mass lost as fat (WL: -7.1 [-8.1, -6.1] kg; -15.9% change from baseline). A differential treatment effect was not observed for change in lean mass (WL: -0.81 [-1.40, -0.23] kg vs WS: -0.24 [-0.85, 0.36] kg). Four-hundred-meter gait speed was also unchanged from baseline although trends suggest slightly increased gait speed in the WL group [0.01 (-0.02, 0.04) m/s] compared with the WS group [-0.02 (-0.05, 0.01) m/s].

Conclusion: Intentional weight loss using a high-protein diet is effective in producing significant total body mass and fat mass loss, while helping preserve lean body mass and mobility, in relatively high-functioning older adults with obesity.
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http://dx.doi.org/10.1093/gerona/gly146DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6521917PMC
May 2019

Achieving advance care planning in diverse, underserved populations.

Nurs Outlook 2018 May - Jun;66(3):311-315. Epub 2018 Apr 11.

Expert Panel on Palliative and End-of-Life Care.

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http://dx.doi.org/10.1016/j.outlook.2018.04.001DOI Listing
February 2019

Physical and Psychological Abuse among Seropositive African American MSM 50 Aged Years and Older.

Issues Ment Health Nurs 2018 Jan 15;39(1):46-52. Epub 2018 Jan 15.

a University of Tennessee Health Science Center , Department Chair & Professor, College of Nursing , Memphis , Tennessee , USA.

Little is known about abuse experienced among African American men who have sex with men (MSM) who are 50 years and older. A series of focus groups were conducted to examine perspectives of seropositive African American MSM age 50 years and older who reported experiencing some form of psychological or physical abuse. Thirty African American MSM were divided into four focus groups and four themes emerged: "Fear Being Gay," "No One Else to Love Me," "Nowhere to Turn," and "Sexual Risk & Control." The data suggest there is a need to develop culturally tailored interventions for this population.
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http://dx.doi.org/10.1080/01612840.2017.1397828DOI Listing
January 2018

Women 50 and Older and HIV: Prevention and Implications for Health Care Providers.

J Gerontol Nurs 2017 Dec 30;43(12):29-34. Epub 2017 Jun 30.

The current article discusses the importance of implementing HIV and AIDS education, prevention, and intervention programs that are tailored to women 50 and older and to determine HIV risk factors for this population. A literature search was performed, resulting in 41 relevant articles. The literature underscored the significance of increasing awareness of HIV/AIDS, particularly among older women. HIV risk behaviors and the effect that these behaviors have on HIV transmission and prevention among women 50 and older are described. Prior research findings identified risk categories of older women that may contribute to the transmission of HIV among this particular population, including heterosexual relations, perceived HIV risk, ageism and HIV transmission, biological factors, transfusions, sexual enhancement aids, and health care providers and prevention messages. In addition, previous findings indicate that health care providers have not traditionally targeted women 50 and older for HIV prevention. Health care providers should incorporate discussion of HIV risk and transmission during clinic visits and implement prevention programs that target this population. [Journal of Gerontological Nursing, 43(12), 29-34.].
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http://dx.doi.org/10.3928/00989134-20170621-01DOI Listing
December 2017

Qualitative Perspectives about Living with HIV from Seropositive African American MSM Aged 50 years and Older.

Issues Ment Health Nurs 2017 Jun 1;38(6):486-492. Epub 2017 Mar 1.

a Institute on Aging, University of Pennsylvania School of Nursing , Philadelphia , Pennsylvania , USA.

It has nearly been more than three decades; yet, the research on aging seropositive African American men who have sex with men (MSM) is scarce. Exploring issues for an aging population of seropositive MSM is critical given that earlier epidemiological data suggested that by 2015, half of the AIDS cases will be in adults aged 50 years and older. A qualitative approach with the aim to examine perspectives about HIV risk from a group of seropositive African American MSM 50 years of age and older was conducted. Two separate focus groups with a total N  =  30 were conducted. Four themes emerged: feeling left out, no place to call home, not a priority, and no one to grow older with.
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http://dx.doi.org/10.1080/01612840.2017.1284969DOI Listing
June 2017

Imaging of Cartilage in the Athlete.

Clin Sports Med 2017 Jul 2;36(3):427-445. Epub 2017 Apr 2.

Department of Radiology, University of Colorado Hospital, 12605 East 16th Avenue, Aurora, CO 80045, USA.

MRI remains the optimal imaging modality to evaluate cartilage injuries in the athlete. As these injuries have no intrinsic healing capacity, early and accurate noninvasive diagnosis remains integral to determining the most appropriate treatment option in this class of patients. Although surgical success depends primarily on clinical outcomes, MRI evaluation can provide pertinent information regarding the status of the surgical repair and the progression of cartilage disease.
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http://dx.doi.org/10.1016/j.csm.2017.02.002DOI Listing
July 2017

Overactive Epidermal Growth Factor Receptor Signaling Leads to Increased Fibrosis after Severe Acute Respiratory Syndrome Coronavirus Infection.

J Virol 2017 06 26;91(12). Epub 2017 May 26.

Department of Microbiology and Immunology, The University of Maryland at Baltimore, Baltimore, Maryland, USA

Severe acute respiratory syndrome coronavirus (SARS-CoV) is a highly pathogenic respiratory virus that causes morbidity and mortality in humans. After infection with SARS-CoV, the acute lung injury caused by the virus must be repaired to regain lung function. A dysregulation in this wound healing process leads to fibrosis. Many survivors of SARS-CoV infection develop pulmonary fibrosis (PF), with higher prevalence in older patients. Using mouse models of SARS-CoV pathogenesis, we have identified that the wound repair pathway, controlled by the epidermal growth factor receptor (EGFR), is critical to recovery from SARS-CoV-induced tissue damage. In mice with constitutively active EGFR [EGFR(DSK5) mice], we find that SARS-CoV infection causes enhanced lung disease. Importantly, we show that during infection, the EGFR ligands amphiregulin and heparin-binding EGF-like growth factor (HB-EGF) are upregulated, and exogenous addition of these ligands during infection leads to enhanced lung disease and altered wound healing dynamics. Our data demonstrate a key role of EGFR in the host response to SARS-CoV and how it may be implicated in lung disease induced by other highly pathogenic respiratory viruses. PF has many causative triggers, including severe respiratory viruses such as SARS-CoV. Currently there are no treatments to prevent the onset or limit the progression of PF, and the molecular pathways underlying the development of PF are not well understood. In this study, we identified a role for the balanced control of EGFR signaling as a key factor in progression to PF. These data demonstrate that therapeutic treatment modulating EGFR activation could protect against PF development caused by severe respiratory virus infection.
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http://dx.doi.org/10.1128/JVI.00182-17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5446658PMC
June 2017

MERS-CoV spike nanoparticles protect mice from MERS-CoV infection.

Vaccine 2017 03 23;35(12):1586-1589. Epub 2017 Feb 23.

University of Maryland, School of Medicine, 685 West Baltimore St, Baltimore, MD 21201, United States. Electronic address:

The Middle East respiratory syndrome coronavirus (MERS-CoV) was first discovered in late 2012 and has gone on to cause over 1800 infections and 650 deaths. There are currently no approved therapeutics or vaccinations for MERS-CoV. The MERS-CoV spike (S) protein is responsible for receptor binding and virion entry to cells, is immunodominant and induces neutralizing antibodies in vivo, all of which, make the S protein an ideal target for anti-MERS-CoV vaccines. In this study, we demonstrate protection induced by vaccination with a recombinant MERS-CoV S nanoparticle vaccine and Matrix-M1 adjuvant combination in mice. The MERS-CoV S nanoparticle vaccine produced high titer anti-S neutralizing antibody and protected mice from MERS-CoV infection in vivo.
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http://dx.doi.org/10.1016/j.vaccine.2017.02.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5423355PMC
March 2017

Health related quality of life and depressive symptoms among seropositive African Americans.

Appl Nurs Res 2017 02 11;33:138-141. Epub 2016 Nov 11.

University of Pennsylvania School of Nursing, Room 222 NEB 418 Curie Blvd, Philadelphia, PA 19104-4217, United States. Electronic address:

The primary aim of this descriptive correlational study was to determine which domains of health related quality of life (HRQOL) after controlling for demographic correlates predict depressive symptoms among N=70 seropositive African American men and women on Active Antiretroviral Therapy (ART). A demographic questionnaire, the Center for Epidemiological Studies Depression Scale (CESD-D), and the SF-36 Health Related Quality of Life (HRQOL) scale were administered. The regression analyses resulted in three models. The first model indicated that emotional well-being explained 38% of the variance in depressive symptoms (P=0.000) and in model two, emotional well-being and role limitations on emotional health explained 50% of the variance (P=0.000) and in the final and best fitting model emotional well-being, role limitations on emotional health and pain explained 53% of the variance in depressive symptoms (P=0.000) respectively. The findings underscore the need to explore the impact of HRQOL on mental health, and to also screen and treat seropositive African American men and women on (ART) for depressive symptoms.
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http://dx.doi.org/10.1016/j.apnr.2016.11.007DOI Listing
February 2017

Predictors of Depression among Seropositive Batswana Men and Women: A Descriptive Correlational Study.

Arch Psychiatr Nurs 2016 12 12;30(6):736-739. Epub 2016 Jul 12.

University of Pennsylvania School of Nursing, Philadelphia, PA. Electronic address:

The purpose of this descriptive correlational study was to describe predictors of depressive symptoms among N=70 seropositive Botswana men and women residing in Gaborne, Botswana. A demographic questionnaire, the Center for Epidemiologic Studies Depression Scale, (CESD-D), and the SF-36 [Quality of life] were administered. The questionnaires were translated and back translated in Setswana and administered by Batswana men and women. The results of the regression analyses resulted in two calculated models. In the first Model energy/fatigue explained 46% of the variance in depressive symptoms (P=.000), and in the second Model energy/fatigue and role limitations on emotional well-being explained 50% of the variance in depressive symptoms respectively. The study findings underscore the need for mental health services for seropositive Batswana men and women.
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http://dx.doi.org/10.1016/j.apnu.2016.07.002DOI Listing
December 2016

One-Health: a Safe, Efficient, Dual-Use Vaccine for Humans and Animals against Middle East Respiratory Syndrome Coronavirus and Rabies Virus.

J Virol 2017 Jan 3;91(2). Epub 2017 Jan 3.

Department of Microbiology and Immunology, Sydney Kimmel Medical College at Thomas Jefferson University, Philadelphia, Pennsylvania, USA

Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012 and is a highly pathogenic respiratory virus. There are no treatment options against MERS-CoV for humans or animals, and there are no large-scale clinical trials for therapies against MERS-CoV. To address this need, we developed an inactivated rabies virus (RABV) that contains the MERS-CoV spike (S) protein expressed on its surface. Our initial recombinant vaccine, BNSP333-S, expresses a full-length wild-type MERS-CoV S protein; however, it showed significantly reduced viral titers compared to those of the parental RABV strain and only low-level incorporation of full-length MERS-CoV S into RABV particles. Therefore, we developed a RABV-MERS vector that contained the MERS-CoV S1 domain of the MERS-CoV S protein fused to the RABV G protein C terminus (BNSP333-S1). BNSP333-S1 grew to titers similar to those of the parental vaccine vector BNSP333, and the RABV G-MERS-CoV S1 fusion protein was efficiently expressed and incorporated into RABV particles. When we vaccinated mice, chemically inactivated BNSP333-S1 induced high-titer neutralizing antibodies. Next, we challenged both vaccinated mice and control mice with MERS-CoV after adenovirus transduction of the human dipeptidyl peptidase 4 (hDPP4) receptor and then analyzed the ability of mice to control MERS-CoV infection. Our results demonstrated that vaccinated mice were fully protected from the MERS-CoV challenge, as indicated by the significantly lower MERS-CoV titers and MERS-CoV and mRNA levels in challenged mice than those in unvaccinated controls. These data establish that an inactivated RABV-MERS S-based vaccine may be effective for use in animals and humans in areas where MERS-CoV is endemic.

Importance: Rabies virus-based vectors have been proven to be efficient dual vaccines against rabies and emergent infectious diseases such as Ebola virus. Here we show that inactivated rabies virus particles containing the MERS-CoV S1 protein induce potent immune responses against MERS-CoV and RABV. This novel vaccine is easy to produce and may be useful to protect target animals, such as camels, as well as humans from deadly MERS-CoV and RABV infections. Our results indicate that this vaccine approach can prevent disease, and the RABV-based vaccine platform may be a valuable tool for timely vaccine development against emerging infectious diseases.
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http://dx.doi.org/10.1128/JVI.02040-16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5215356PMC
January 2017

CD8+ T Cells and Macrophages Regulate Pathogenesis in a Mouse Model of Middle East Respiratory Syndrome.

J Virol 2017 Jan 16;91(1). Epub 2016 Dec 16.

Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland, USA

Middle East respiratory syndrome coronavirus (MERS-CoV) is an important emerging pathogen that was first described in 2012. While the cell surface receptor for MERS-CoV has been identified as dipeptidyl peptidase 4 (DPP4), the mouse DPP4 homologue does not allow virus entry into cells. Therefore, development of mouse models of MERS-CoV has been hampered by the fact that MERS-CoV does not replicate in commonly available mouse strains. We have previously described a mouse model in which mDPP4 was replaced with hDPP4 such that hDPP4 is expressed under the endogenous mDPP4 promoter. In this study, we used this mouse model to analyze the host response to MERS-CoV infection using immunological assays and transcriptome analysis. Depletion of CD4 T cells, CD8 T cells, or macrophages has no effect on MERS-CoV replication in the lungs of infected mice. However, we found that depletion of CD8 T cells protects and depletion of macrophages exacerbates MERS-CoV-induced pathology and clinical symptoms of disease. Overall, we demonstrate an important role for the inflammatory response in regulating MERS-CoV pathogenesis in vivo IMPORTANCE: The Middle East respiratory syndrome coronavirus (MERS-CoV) is a highly pathogenic respiratory virus that emerged from zoonotic sources in 2012. Human infections are still occurring throughout Saudi Arabia at a 38% case fatality rate, with the potential for worldwide spread via air travel. In this work, we identify the host response to the virus and identify inflammatory pathways and cell populations that are critical for protection from severe lung disease. By understanding the immune response to MERS-CoV we can develop targeted therapies to inhibit pathogenesis in the future.
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http://dx.doi.org/10.1128/JVI.01825-16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5165197PMC
January 2017

Correlates of Condom Use Among Substance Using Older Seropositive MSM: Implications for Mental Health Practice.

Issues Ment Health Nurs 2016 Oct 12;37(10):727-733. Epub 2016 Aug 12.

a School of Nursing , University of Pennsylvania , Philadelphia , Pennsylvania.

The purpose of this study was to describe the correlates of condom use among a sample of N = 60 substance using seropositive men who have sex with (MSM). The mean age of the study participants was 52 ranging 50-75 years of age. Seventy-percent of study participants reporting smoking marijuana, 62% using cocaine, 25% heroin, 37% alcohol, and 30% amphetamines. Among those reporting substance use, 75% reported it was a hassle to use condoms, 42% indicated pleasure decreased with condom use, 72% indicated safer sex is boring, 72% reported the idea of using condoms is unappealing, 78% reported condoms ruined sex, and 71% said condoms interfered with romance. A multiple logistic regression analysis revealed low self-esteem, relationship status, attitudes towards condom use, and depression predicted condom use χ = 20.79, df = 6, ρ =.002. The study findings have implications for mental health nursing practice with seropositive African American MSM.
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http://dx.doi.org/10.1080/01612840.2016.1212293DOI Listing
October 2016

Abelson Kinase Inhibitors Are Potent Inhibitors of Severe Acute Respiratory Syndrome Coronavirus and Middle East Respiratory Syndrome Coronavirus Fusion.

J Virol 2016 10 12;90(19):8924-33. Epub 2016 Sep 12.

Department of Microbiology and Immunology, University of Maryland, Baltimore, Maryland, USA

Unlabelled: The highly pathogenic severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) cause significant morbidity and morality. There is currently no approved therapeutic for highly pathogenic coronaviruses, even as MERS-CoV is spreading throughout the Middle East. We previously screened a library of FDA-approved drugs for inhibitors of coronavirus replication in which we identified Abelson (Abl) kinase inhibitors, including the anticancer drug imatinib, as inhibitors of both SARS-CoV and MERS-CoV in vitro Here we show that the anti-CoV activity of imatinib occurs at the early stages of infection, after internalization and endosomal trafficking, by inhibiting fusion of the virions at the endosomal membrane. We specifically identified the imatinib target, Abelson tyrosine-protein kinase 2 (Abl2), as required for efficient SARS-CoV and MERS-CoV replication in vitro These data demonstrate that specific approved drugs can be characterized in vitro for their anticoronavirus activity and used to identify host proteins required for coronavirus replication. This type of study is an important step in the repurposing of approved drugs for treatment of emerging coronaviruses.

Importance: Both SARS-CoV and MERS-CoV are zoonotic infections, with bats as the primary source. The 2003 SARS-CoV outbreak began in Guangdong Province in China and spread to humans via civet cats and raccoon dogs in the wet markets before spreading to 37 countries. The virus caused 8,096 confirmed cases of SARS and 774 deaths (a case fatality rate of ∼10%). The MERS-CoV outbreak began in Saudi Arabia and has spread to 27 countries. MERS-CoV is believed to have emerged from bats and passed into humans via camels. The ongoing outbreak of MERS-CoV has resulted in 1,791 cases of MERS and 640 deaths (a case fatality rate of 36%). The emergence of SARS-CoV and MERS-CoV provides evidence that coronaviruses are currently spreading from zoonotic sources and can be highly pathogenic, causing serious morbidity and mortality in humans. Treatment of SARS-CoV and MERS-CoV infection is limited to providing supportive therapy consistent with any serious lung disease, as no specific drugs have been approved as therapeutics. Highly pathogenic coronaviruses are rare and appear to emerge and disappear within just a few years. Currently, MERS-CoV is still spreading, as new infections continue to be reported. The outbreaks of SARS-CoV and MERS-CoV and the continuing diagnosis of new MERS cases highlight the need for finding therapeutics for these diseases and potential future coronavirus outbreaks. Screening FDA-approved drugs streamlines the pipeline for this process, as these drugs have already been tested for safety in humans.
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http://dx.doi.org/10.1128/JVI.01429-16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5021412PMC
October 2016

Risk Factors for and Barriers to Control Type-2 Diabetes among Saudi Population.

Glob J Health Sci 2016 9 1;8(9):54089. Epub 2016 Sep 1.

.

Background: The prevalence of Type-2 Diabetes is dramatically increasing in urban areas within Saudi Arabia. Hence, Type-2 Diabetes has now become the most common public health problem. Understanding the major risk factors for and barriers to control Type-2 Diabetes may lead to strategies to prevent, control, and reduce in the burden of disease cases.

Objective: To describe risk factors for and barriers to control Type- 2 Diabetes in Saudi Arabia.

Methods: The literature search was conducted on risk factors for and barriers to control Type- 2 Diabetes in Saudi Arabia using the databases PubMed, MEDLINE, and Google Scholar (2007-2015). The literature search yielded 80 articles, of which 70 articles were included in this review after excluding non-relevant articles. 

Results: The literature review revealed that obesity, physical inactivity, unhealthy diet, smoking, and aging are the major risk factors for Type-2 Diabetes in Saudi Arabia. Further, the review allocated a complex set of barriers including, lack of education, social support, and healthy environment. These barriers may hinder Saudis with Type-2 Diabetes from controlling their disease.

Conclusion: The prevalence of Type-2 Diabetes is high among the Saudi population and represents a major public health problem. Effective research programs are needed to address the modifiable risk factors for and barriers to control Type-2 Diabetes among Saudi population.
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http://dx.doi.org/10.5539/gjhs.v8n9p10DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5064063PMC
September 2016

Human polyclonal immunoglobulin G from transchromosomic bovines inhibits MERS-CoV in vivo.

Sci Transl Med 2016 Feb;8(326):326ra21

Department of Microbiology and Immunology, University of Maryland, School of Medicine, Baltimore, MD 21201, USA.

As of 13 November 2015, 1618 laboratory-confirmed human cases of Middle East respiratory syndrome coronavirus (MERS-CoV) infection, including 579 deaths, had been reported to the World Health Organization. No specific preventive or therapeutic agent of proven value against MERS-CoV is currently available. Public Health England and the International Severe Acute Respiratory and Emerging Infection Consortium identified passive immunotherapy with neutralizing antibodies as a treatment approach that warrants priority study. Two experimental MERS-CoV vaccines were used to vaccinate two groups of transchromosomic (Tc) bovines that were genetically modified to produce large quantities of fully human polyclonal immunoglobulin G (IgG) antibodies. Vaccination with a clade A γ-irradiated whole killed virion vaccine (Jordan strain) or a clade B spike protein nanoparticle vaccine (Al-Hasa strain) resulted in Tc bovine sera with high enzyme-linked immunosorbent assay (ELISA) and neutralizing antibody titers in vitro. Two purified Tc bovine human IgG immunoglobulins (Tc hIgG), SAB-300 (produced after Jordan strain vaccination) and SAB-301 (produced after Al-Hasa strain vaccination), also had high ELISA and neutralizing antibody titers without antibody-dependent enhancement in vitro. SAB-301 was selected for in vivo and preclinical studies. Administration of single doses of SAB-301 12 hours before or 24 and 48 hours after MERS-CoV infection (Erasmus Medical Center 2012 strain) of Ad5-hDPP4 receptor-transduced mice rapidly resulted in viral lung titers near or below the limit of detection. Tc bovines, combined with the ability to quickly produce Tc hIgG and develop in vitro assays and animal model(s), potentially offer a platform to rapidly produce a therapeutic to prevent and/or treat MERS-CoV infection and/or other emerging infectious diseases.
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http://dx.doi.org/10.1126/scitranslmed.aaf1061DOI Listing
February 2016

Severe Acute Respiratory Syndrome Coronavirus ORF7a Inhibits Bone Marrow Stromal Antigen 2 Virion Tethering through a Novel Mechanism of Glycosylation Interference.

J Virol 2015 Dec 16;89(23):11820-33. Epub 2015 Sep 16.

Department of Microbiology and Immunology, University of Maryland at Baltimore, Baltimore, Maryland, USA

Unlabelled: Severe acute respiratory syndrome (SARS) emerged in November 2002 as a case of atypical pneumonia in China, and the causative agent of SARS was identified to be a novel coronavirus, severe acute respiratory syndrome coronavirus (SARS-CoV). Bone marrow stromal antigen 2 (BST-2; also known as CD317 or tetherin) was initially identified to be a pre-B-cell growth promoter, but it also inhibits the release of virions of the retrovirus human immunodeficiency virus type 1 (HIV-1) by tethering budding virions to the host cell membrane. Further work has shown that BST-2 restricts the release of many other viruses, including the human coronavirus 229E (hCoV-229E), and the genomes of many of these viruses encode BST-2 antagonists to overcome BST-2 restriction. Given the previous studies on BST-2, we aimed to determine if BST-2 has the ability to restrict SARS-CoV and if the SARS-CoV genome encodes any proteins that modulate BST-2's antiviral function. Through an in vitro screen, we identified four potential BST-2 modulators encoded by the SARS-CoV genome: the papain-like protease (PLPro), nonstructural protein 1 (nsp1), ORF6, and ORF7a. As the function of ORF7a in SARS-CoV replication was previously unknown, we focused our study on ORF7a. We found that BST-2 does restrict SARS-CoV, but the loss of ORF7a leads to a much greater restriction, confirming the role of ORF7a as an inhibitor of BST-2. We further characterized the mechanism of BST-2 inhibition by ORF7a and found that ORF7a localization changes when BST-2 is overexpressed and ORF7a binds directly to BST-2. Finally, we also show that SARS-CoV ORF7a blocks the restriction activity of BST-2 by blocking the glycosylation of BST-2.

Importance: The severe acute respiratory syndrome coronavirus (SARS-CoV) emerged from zoonotic sources in 2002 and caused over 8,000 infections and 800 deaths in 37 countries around the world. Identifying host factors that regulate SARS-CoV pathogenesis is critical to understanding how this lethal virus causes disease. We have found that BST-2 is capable of restricting SARS-CoV release from cells; however, we also identified a SARS-CoV protein that inhibits BST-2 function. We show that the SARS-CoV protein ORF7a inhibits BST-2 glycosylation, leading to a loss of BST-2's antiviral function.
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http://dx.doi.org/10.1128/JVI.02274-15DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4645327PMC
December 2015

Growth and Quantification of MERS-CoV Infection.

Curr Protoc Microbiol 2015 May 1;37:15E.2.1-9. Epub 2015 May 1.

University of Maryland School of Medicine, Microbiology and Immunology, Baltimore, Maryland.

Middle East respiratory syndrome coronavirus (MERS-CoV) is an emerging highly pathogenic respiratory virus. Although MERS-CoV only emerged in 2012, we and others have developed assays to grow and quantify infectious MERS-CoV and RNA products of replication in vitro. MERS-CoV is able to infect a range of cell types, but replicates to high titers in Vero E6 cells. Protocols for the propagation and quantification of MERS-CoV are presented.
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http://dx.doi.org/10.1002/9780471729259.mc15e02s37DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4735735PMC
May 2015

Effectiveness of a Medifast meal replacement program on weight, body composition and cardiometabolic risk factors in overweight and obese adults: a multicenter systematic retrospective chart review study.

Nutr J 2015 Aug 6;14:77. Epub 2015 Aug 6.

Department of Scientific and Clinical Affairs, Medifast, Inc, 11445 Cronhill Drive, Owings Mills, MD, 21117, USA.

Background: Recent medical guidelines emphasize the importance of actively treating overweight and obesity with diet and lifestyle intervention to achieve ≥ 5% weight loss in a 6-month period. Commercial programs offer one approach provided there is evidence of their efficacy and safety. This study was conducted to evaluate the effectiveness of the Medifast® 4 & 2 & 1 Plan™ on weight loss, body composition and cardiometabolic risk factors in overweight and obese adults.

Methods: A systematic retrospective chart review of 310 overweight and obese clients following the Medifast 4 & 2 & 1 Plan at one of 21 Medifast Weight Control Centers® was conducted. Data were recorded electronically and key data points were independently verified. The primary endpoint was change from baseline body weight at 12 weeks. Within group paired t-tests were used to examine changes from baseline in a completers population. Differences between gender and age subgroups were examined using bivariate t-tests and mixed model regression analyses.

Results: For the primary endpoint at 12 weeks, body weight among completers (n = 185) was reduced by a mean of 10.9 ± 5.6 kg (-10.1%, p < 0.0001), and at 24 weeks (n = 81) mean weight was reduced by 16.0 ± 7.9 kg (-14.3%). At 12 and 24 weeks, 85% and 96% of those remaining on the plan, respectively, had lost ≥ 5% of their baseline body weight. Lean mass was preserved to within 5% of baseline throughout the 24 weeks, and fat mass represented ≥ 80% of the body weight lost from 12 weeks onward. Men, women, seniors (≥ 65 years), and non-seniors (<65 years) all had significant weight reductions with preservation of lean mass. Significant improvements in blood pressure, pulse and waist-to-hip ratio were observed. Mean weight regain among the subset who entered a formal maintenance phase was <2% during an average follow-up of 34 weeks. The meal plan was well tolerated, and program adherence was >85%.

Conclusions: The 4 & 2 & 1 Plan used at Medifast Weight Control Centers was effective for weight loss, preservation of lean mass and improvement in cardiometabolic risk factors. The plan was generally well tolerated in a broad population of overweight and obese adults. #NCT02150837.
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http://dx.doi.org/10.1186/s12937-015-0062-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4527127PMC
August 2015

Pre- and postexposure efficacy of fully human antibodies against Spike protein in a novel humanized mouse model of MERS-CoV infection.

Proc Natl Acad Sci U S A 2015 Jul 29;112(28):8738-43. Epub 2015 Jun 29.

Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591;

Traditional approaches to antimicrobial drug development are poorly suited to combatting the emergence of novel pathogens. Additionally, the lack of small animal models for these infections hinders the in vivo testing of potential therapeutics. Here we demonstrate the use of the VelocImmune technology (a mouse that expresses human antibody-variable heavy chains and κ light chains) alongside the VelociGene technology (which allows for rapid engineering of the mouse genome) to quickly develop and evaluate antibodies against an emerging viral disease. Specifically, we show the rapid generation of fully human neutralizing antibodies against the recently emerged Middle East Respiratory Syndrome coronavirus (MERS-CoV) and development of a humanized mouse model for MERS-CoV infection, which was used to demonstrate the therapeutic efficacy of the isolated antibodies. The VelocImmune and VelociGene technologies are powerful platforms that can be used to rapidly respond to emerging epidemics.
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http://dx.doi.org/10.1073/pnas.1510830112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4507189PMC
July 2015

Considerations for implementing oral preexposure prophylaxis: a literature review.

J Assoc Nurses AIDS Care 2014 Nov-Dec;25(6):496-507. Epub 2014 Jul 27.

Oral preexposure prophylaxis (PrEP) is in its infancy as an approved biomedical intervention; therefore, research is needed to understand the issues surrounding its implementation. The purpose of this literature review is to report the empirical research about PrEP to identify the salient issues surrounding its implementation. PubMed, Medline, and CINAHL databases were searched, yielding 45 articles meeting inclusion criteria for the review. Overall, we found patient awareness of PrEP varied and its use was low. Awareness was higher among providers. Patients were willing to use PrEP, but both patients' and providers' concerns may have impacted implementation of this intervention. PrEP requires a prescription, yet only five of the 45 articles addressed provider-level factors. Research involving providers is needed to ensure that patient risk of becoming infected with HIV is accurately assessed, that PrEP is provided to those at high risk for HIV infection, and that frequent follow-up is conducted.
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http://dx.doi.org/10.1016/j.jana.2014.07.005DOI Listing
August 2015

Treating MERS-CoV during an outbreak.

Lancet Infect Dis 2014 Nov 29;14(11):1030-1031. Epub 2014 Sep 29.

Department of Microbiology and Immunology, University of Maryland at Baltimore, Baltimore, MD 21201, USA. Electronic address:

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http://dx.doi.org/10.1016/S1473-3099(14)70939-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7128167PMC
November 2014

Repurposing of clinically developed drugs for treatment of Middle East respiratory syndrome coronavirus infection.

Antimicrob Agents Chemother 2014 Aug 19;58(8):4885-93. Epub 2014 May 19.

Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland, USA

Outbreaks of emerging infections present health professionals with the unique challenge of trying to select appropriate pharmacologic treatments in the clinic with little time available for drug testing and development. Typically, clinicians are left with general supportive care and often untested convalescent-phase plasma as available treatment options. Repurposing of approved pharmaceutical drugs for new indications presents an attractive alternative to clinicians, researchers, public health agencies, drug developers, and funding agencies. Given the development times and manufacturing requirements for new products, repurposing of existing drugs is likely the only solution for outbreaks due to emerging viruses. In the studies described here, a library of 290 compounds was screened for antiviral activity against Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus (SARS-CoV). Selection of compounds for inclusion in the library was dependent on current or previous FDA approval or advanced clinical development. Some drugs that had a well-defined cellular pathway as target were included. In total, 27 compounds with activity against both MERS-CoV and SARS-CoV were identified. The compounds belong to 13 different classes of pharmaceuticals, including inhibitors of estrogen receptors used for cancer treatment and inhibitors of dopamine receptor used as antipsychotics. The drugs identified in these screens provide new targets for in vivo studies as well as incorporation into ongoing clinical studies.
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http://dx.doi.org/10.1128/AAC.03036-14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4136000PMC
August 2014

Evaluation of SSYA10-001 as a replication inhibitor of severe acute respiratory syndrome, mouse hepatitis, and Middle East respiratory syndrome coronaviruses.

Antimicrob Agents Chemother 2014 Aug 19;58(8):4894-8. Epub 2014 May 19.

Christopher Bond Life Sciences Center, University of Missouri, Columbia, Missouri, USA Department of Molecular Microbiology & Immunology, University of Missouri School of Medicine, Columbia, Missouri, USA Department of Biochemistry, University of Missouri, Columbia, Missouri, USA

We have previously shown that SSYA10-001 blocks severe acute respiratory syndrome coronavirus (SARS-CoV) replication by inhibiting SARS-CoV helicase (nsp13). Here, we show that SSYA10-001 also inhibits replication of two other coronaviruses, mouse hepatitis virus (MHV) and Middle Eastern respiratory syndrome coronavirus (MERS-CoV). A putative binding pocket for SSYA10-001 was identified and shown to be similar in SARS-CoV, MERS-CoV, and MHV helicases. These studies show that it is possible to target multiple coronaviruses through broad-spectrum inhibitors.
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http://dx.doi.org/10.1128/AAC.02994-14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4136041PMC
August 2014
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